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et al. of Pharmacy and Pharmaceutical Sciences
InternationalDesai
Journal
Int J Pharm Pharm Sci, Vol 5, Issue 1, 160-163
ISSN- 0975-1491
Vol 5, Issue 1, 2013
Research Article
A STUDY OF ADVERSE DRUG REACTIONS IN PATIENTS ADMITTED TO INTENSIVE CARE UNIT
OF A TERTIARY CARE TEACHING RURAL HOSPITAL
JAYESH M KATHIRIA, BHAGYA M SATTIGERI, *PARTH M DESAI, SUMIT P PATEL
Department of Pharmacology, S.B.K.S. Medical Institute and Research Centre, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat-391760.
Email: [email protected]
Received: 11 Oct 2012, Revised and Accepted: 16 Nov 2012
ABSTRACT
Adverse drug reactions (ADRs) are the common problems faced in the setups like ICU where the poly pharmacy is involved in treating the patients.
Control of such events is possible if the culpable drug is known or if it is identified and reported. However, reporting of adverse drug reactions still
remains in its infancy for problems in many. Awareness about adverse drug reactions can decrease irrational use of medicines, poly pharmacy and
adverse drug-drug interactions.
A prospective, observational and non-interventional study was conducted over a period of 18 months in medical ICU of Dhiraj hospital, Piparia with
the goal to highlight the responsibility of health care professionals in preventing, identifying, diagnosis, treating and reporting ADRs. The patients
were monitored daily for ADRs. The data was analyzed for demographic parameters. The causality relationship between suspected drugs and the
reactions were assessed by using various standard causality assessment scales.
1000 patients were enrolled for the study. Out of these 45 patients developed ADRs. Of these 27 males and 18 females developed ADRs showing
male predominance (2.7%). The ADRs increased with increasing number of drugs administered. The drug class most commonly implicated with
ADRs was antibiotics 24(53.33%).The system most commonly involved with an ADR was gastrointestinal tract 26.67%. Most commonly reported
reaction were hypoglycemia (13.33%) and Rash (11.11%).
INTRODUCTION
Although health care personnel are for patient’s safety, mistakes and
errors inevitably occur, particularly in a complex environment such
as the Intensive Care Unit (ICU) [1]. Such errors have serious
implication for patients well being, are costly for safety and are a
major public motivation to strive for a safer health care system [2].
One factor that influences morbidity and mortality is a harmful,
unpredicted reaction to a drug, an almost daily occurrence in
hospitals. The ICU has been known to be the land of polypharmacy
for many years. Polypharmacy is known to increase the risk of
adverse drug reaction (ADRs), drug-drug and drug-disease
interaction. It has been claimed that patients taking two drugs face a
13% risk of adverse drug interactions, rising to 38 % when taking
four drugs and to 82 % if seven or more drugs are given
simultaneously [3].
Adverse drug reactions (ADR) can occur at any stage of the treatment.
Only 25% of ADR are either unpredictable or caused by an allergic
reaction. In most instances (>70%) of ADR are related to dose of drug
administered [4]. The critically ill patients in ICU are more vulnerable
to ADR than others. Moreover, administration of multiple drugs, a
common event in ICU leads to an increased incidence of ADR [5]. The
incidence is variable and has been reported to be as high as 29.7 per
100 admissions in some medical centres [6].
ADRs are complex issues, which require special attention. They
involve patients, medical professionals, pharmaceutical industries,
drug regulatory agencies and academic scientists. Avoidable adverse
effects will be reduced by more skillfull prescription by doctors after
understanding their patients and their diseases.
In this backdrop the study was undertaken to;
•
Measure the incidence, types and nature of ADR, drugs causing
the same in patients admitted in Medical ICU at Dhiraj Hospital, a
tertiary care teaching rural hospital, Piparia, Vadodara.
•
Highlight the responsibility of health care professionals in
preventing, identifying, diagnosing, treating and reporting ADRs.
MATERIALS AND METHODS
A prospective, observational and non-interventional study was
carried out in the medical ICU, in department of medicine, at Dhiraj
Hospital in serially admitted patients over a period of 18 months. A
total of 1000 patients were enrolled and the data was analyzed
statistically. Patients with ADR, as a result of drugs initiated or
continued in medical ICU were included in the study while, the
patients with the community acquired ADR who were treated in
medical ICU were excluded. The medical ICU was visited daily.
Patients drug charts, medical & nursing notes and any evidence of
ADR were noted. The patients who developed ADR were closely
observed.
Patients of age 18 years and above, of either sex, who stayed more
than 24 hours in medical intensive care units and patients
developing ADRs in the medical intensive care units was included in
the study.
Patients referred by or transferred from other department,
discharged or transferred to other department within 24 hours of
admission, community acquired ADR patients, patients who are
uncooperative and patients who are not willing to participate in
study were excluded from the study.
Objective markers of ADR (e.g. laboratory results are recorded from
patient file) and subjective markers of ADR for example headache,
nausea, rashes etc. were identified by history and patient’s
examination. Suspected ADRs were classified in terms of causality,
severity and probability according to WHO, Hartwig and Naranjo
scale respectively. They were assessed for suitability for White card
reporting and classified as either Type A or Type B. Length of stay
for each patient with ADR was recorded. Whether the ADR directly
increased the length of stay was also observed. Patient information
about age, sex & brief medical history, information about drugs like
name (brand/ingredient and manufacture), dose, route, duration of
therapy, indication, and start/stop dates were recorded in case
record form.
Description of adverse drug reaction like its character, localization &
severity was noted. The risk factors (e.g. impaired renal function,
previous exposure to suspected drug, previous allergy, and social
drug use) were identified and were recorded in ADR reporting form.
The patients willing to participate in the study were explained about
the purpose and method of the study in the language they
understood and only those patients were enrolled, who were willing
to give a written consent in the informed consent form.
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Confidentiality in respect to participating patients was maintained at
all levels.
Collection of data
Information of all the patients admitted to the medical ICU, including
relevant history, examination details, investigations and drug
therapy was collected and recorded in the case record form. Any
adverse drug reaction observed by the investigator or treating
physician was noted in the adverse drug reaction reporting form. In
this study only adverse drug reactions were monitored. No
observations/remarks were made on the diagnosis or management
of the patient. All the patients meeting the inclusion criteria were
included in the study and were serially analyzed. The study was
conducted on approval of the Institutional Ethics Committee
Data obtained included the ADRs that occurred in patients of either
sex, of different age groups, the type of ADRs that occurred, the
incident and the body system that was affected. ADRs were graded
according to WHO-UMC criteria, their severity was analysed
according to Hartwig scale and probability was assessed according
to Naranjo scale.
RESULTS
A total of 1000 patients admitted to the medical ICU in a rural
hospital during the study period of 18 months were enrolled for the
study. Of the enrolled patients 665 were male and 335 were female
patients.
A total of 45 patients (4.5%) suffered from ADRs of different types,
of which 27(2.7%) were male patients and 18 (1.8%) were female
patients. When assessed according to their ages we observed that
the percentage of ADR was more common in patients aged between
41-50 years which showed 31.11% of ADR, while patients between
51-60 years showed 24.44% and the elderly patients above 60 years
showed 22.22% of ADR, whereas patients between 31-40 years
showed 15.55% and the occurrence of ADR was observed to be least
in patients with age group of 18-30 years which was 6.66% (figure
1)
In our study we observed that of the enrolled patients, 45 patients
belonging to either sex suffered with ADRs, 75.5% were of type A
reactions(predictable type) and 24.5% were of type B
reactions(unpredictable type) (figure 2).
Fig. 1: Total percentage of ADRs in the patients enrolled (including both genders), grouped according to their ages.
Fig. 2: Percentage of different types of Adverse Drug Reactions
We have observed that gastrointestinal system was most commonly
affected (26.67%) followed by blood and skin (20% each). Other
systems involved included, central nervous system (15.56%),
musculoskeletal (8.89%) and cardiovascular system (6.67%). The
least system affected with adverse drug reactions was respiratory
system (2.22%) (Table 1)
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Table 1: System associated with adverse drug reactions
Systems involved
Gastrointestinal
Blood
Skin
Central nervous system
Musculoskeletal system
Cardiovascular
Respiratory
No. of ADRs(n=45)
12
9
9
7
4
3
1
Of the different groups of drugs that were administered to the patients
at the time of treatment in the medical ICU, antimicrobials (53.33%)
were the drugs which were most involved in causing adverse drug
reactions, followed by antidiabetics (13.33%). Other groups involved
Percentage (%)
26.67
20.00
20.00
15.56
8.89
6.67
2.22
included, whole blood and related drugs (8.89%) each, diuretics
(6.67%), analgesic (6.67%) and drugs of autonomic nervous system
(6.67%). The least implicated groups were antimalarials (4.44%),
laxatives (4.44%) and anti-tubercular drugs (4.44%). (Table 2)
Table 2: Drug classes and drugs involved in adverse drug reactions
Drug classes
Anti microbial drugs
Ceftriaxone
Levofloxacin
Cefoperazone
Sulbactum
Metronidazole
Amoxicillin
Doxycyclin
Ciprofloxacin
Cefotaxim
Ampicillin
Autonomic nervous system
Atropine
Dobutamine
Antimalarials
Chloroquine
Artesunate
Vitamins
Vitamin K
Vaccines
Hepatitis B vaccine
Number of ADRs(%)
24(53.33)
4
3
2
2
4
1
2
3
2
1
3(6.67)
2
1
2(4.44)
1
1
1(2.22)
1
1(2.22)
1
DISCUSSION
Adverse drug reactions (ADRs) are global problems and are of major
concern, affecting patients of either sex and patients belonging to all
age groups. They impose considerable economic burden on the
society and the already stretched health-care systems [7]. The
administered drugs can produce predictable but tolerable toxic side
effects at therapeutic doses which are related to their pharmacology.
In addition, unpredictable toxicity can occur which is unrelated to
the pharmacological actions of these compounds. Although there are
many problems which can be associated with the introduction of
drugs to human bodies, ADRs represent a major drug related
problems [9].
Regrettably, the adverse reactions to the medication are
generally not well studied and the mechanism of some in causing
the ADRs remains poorly described. The problem is further
exacerbated by the inadequate training that clinicians receive in
the basic principle of applied pharmacology and therapeutics.
The adverse drug events may be attributable to the drugs,
diagnostic agents, the biologicals, nutrients, fluids, electrolytes, a
pharmaceutical excipient or even the common components of
the drug delivery systems. Occasionally more than one agent is
involved in causing the ADRs regardless of the route and mode of
drug administration.
Often the adverse drug reactions are not recognized and go
unreported. The principle limitation of ADR detection is the lack of
awareness, of, what constitutes an ADR. Most of the ADRs are
brought to medical attention by subjective reports and patients
complaints.
Drug classes
Antidiabetic drugs
Insulin
Blood & related drugs
Whole blood
Streptokinase
Enoxaparin
Diuretic s
Mannitol
Furosemide
Torsemide
Analgesics
Aspirin
Tramadol
Laxatives
Liquid paraffin & milk of magnesia
Corticosteroids
Budesonide
Antitubercular drugs
Pyrazinamide
Cycloserin
Intravenous fluids
Number of ADRs (%)
6(3.33)
6
4(8.89)
2
1
1
3(6.67)
1
1
1
3(6.67)
2
1
2(4.44)
2
1(2.22)
1
2(4.44)
1
1
1(2.22)
Therefore it is important to determine the presence of ADRs for the
following three reasons:
1) To take immediate action on particular patients, 2) To take action
to prevent future accident in patients in general, and 3) To avoid
medico-legal problems or negligence litigation.
The post marketing surveillance of drugs is very important in
analyzing and managing the risks associated with drugs once they
are available for the use of the general population. Spontaneous
reporting of ADRs has contributed significantly to successful
pharmacovigilance. The health professional’s contribution in this
regard, has encouraged ongoing ascertainment of the benefit risk
ratio of some drugs as well as detection of unsuspected and unusual
ADRs those were previously undetected during the initial evaluation
of a drug. Inspite of these, under-reporting of the adverse drug
reactions remains a major draw-back. It is estimated that only 6–
10% of all ADRs are reported. In some of the developing countries it
might be very difficult to attribute the adverse reactions to a
particular drug. This may be due to the cultural attitude of many
people who use obscure indigenous drugs, practice self-medication,
and go from one doctor to another doctor.
With multiple drugs used for the patients admitted in medical ICU,
the ADRs were more common with the antimicrobial agents
followed by antidiabetic medications, blood and related drugs that
occurred in the form of hypoglycemia, rashes, itching, dizziness,
diarrhoea, vomiting, abdominal pain, epigastric distress, joint pain
etc. The elderly populations are at high risk because of the number
of medications consumed, complicated drug regimens, and clinical
states often presented. About 80% of elderly patients routinely take
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prescription and non-prescription medications concurrently. Some
patients may see multiple physicians for acute and chronic
conditions, as well as obtain medication from more than one
community pharmacy or mail-order pharmacy [9].
The elderly populations are at high risk because of By the causality
assessment of ADRs according to the WHO criteria, that, of the 45
occurred adverse drug reactions, most of ADRs were possible
(51.11%) and probable (40%) in nature and some of them were
certain (4.44%).
According to severity assessment scale of Hartwig, of the 45 adverse
drug reactions 35.56% of adverse drug reactions were in level-2 and
level-3 each and 28.89% of adverse drug reactions were in level-1.
So that 29 (64.45%) of ADRs were mild in nature while 16 (35.56%)
of ADRs were moderate in nature.
recorded case of ADR. 75.5% were predictable and 24.5% of them
were unpredictable type of ADRs.
ACKNOWLEDGEMENT
The authors are thankful to S.B.K.S Medical Institute and Research
Centre, Sumandeep Vidyapeeth, Vadodara, India for providing
necessary facilities throughout this work.
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